Lithium enolates constitute one of the most important classes of reactive intermediate in organic synthesis. The pharmaceutical industry uses these reagents frequently and on very large scales. In this proposal we describe efforts to understand the underlying chemistry of the most important reactions of lithium enolates. We will focus on ascertaining key structure-reactivity relationships for a number of enolates including enolates derived from simple esters and ketones, beta-amino-esters, chiral carboxamides based on oxazolidinone and ephedrate auxiliaries (Evans and Myers enolates), N-methoxycarboxamides (Weinreb amides), and alpha fluoro esters. The lithium salts of chiral vicinal amino alkoxides will also be investigated. Given the limited progress toward understanding solution structures of lithium enolates reported to date, considerable effort will focus on developing and refining new methods of structure determination. The relationships of structure and reactivity will derive from case studies to be investigated including (1) alkylation, (2) acylation, (3) azaaldol condensation, and (4) nucleophilic aromatic substitution. Through an understanding of the mechanistic principles we learn to control reactivity and selectivity via a uniquely integrated approach based on a combination of NMR spectroscopy, solution kinetics, and computational chemistry. By bringing synthetic organic, physical organic, analytical, and computational chemistry together under one roof, we reveal the consequences of solvation and aggregation with an unprecedented clarity. [unreadable] [unreadable] [unreadable]